Gene silencing has emerged as a promising strategy for molecular therapy of various malignant, viral, hereditary and inflammatory disorders. However, its translation from lab to clinic is yet to gain momentum due to the numerous problems that plague its development. A multi-functional siRNA delivery system with desired properties such as enhanced immune compatibility, target specificity, high cell uptake and excellent silencing efficiency is required to understand the challenges involved in the selection and modification of small interfering RNA (siRNA), factors influencing the complexation process and the response of the biological system to the formulation. Liposomes have been used as delivery systems due to its versatility in handling different types of drugs, tunable size, charge and surface functionalities that improve its effectiveness in vivo. This review highlights the challenges involved in gene silencing and describes the progression of liposomal systems used in gene silencing. The rationale in introducing chemical modifications in siRNA, synthesizing designer cationic lipids and evolution of hybrid liposomal systems has been elaborated, emphasizing their merits and short-comings. Finally, a description of the current state of clinical trials involving liposomal formulations has been included to provide an unbiased perspective of the future of liposomal systems and gene silencing tools as therapeutic tools.
Nano-delivery systems have significantly evolved over the last decade for the treatment of cancer by enabling site-specific delivery and improved bioavailability. The widely investigated nanoparticle systems are biodegradable polyesters, dendrimers, liposomes, mesoporous silica and gold nanoparticles. These particles when conjugated with different targeting motifs enhance the therapeutic efficiency of the drug molecules and biocompatibility. However, the application of such systems towards the treatment of retinoblastoma (RB), a rapidly spreading childhood eye cancer, still remains in its infancy. Nanoparticle-based systems that have been investigated for RB therapy have displayed improved drug delivery to the most restricted posterior segment of the eyes and have increased intra-vitreal half-life of the chemotherapy agents highlighting its potential in treatment of this form of cancer. This review focuses on the challenges involved in the treatment of RB and highlights the attempts made to develop nano-dimensional systems for the treatment of RB.
Multifunctional nanoparticles are next generation materials that can be simultaneously used for imaging, diagnosis, and delivery of drugs. However, materials intended for cancer diagnosis need to be investigated for its cell uptake, toxicity, and effectiveness. In the current work, we have synthesized fluorescent iron oxide nanoparticles and evaluated its efficacy against retinoblastoma cell imaging. The iron oxide nanoparticles were synthesized and stabilized using oleic acid. Sulforhodamine B was adsorbed onto albumin over the oleic acid-capped iron oxide nanoparticles. Our results demonstrated good cell uptake in a time-dependent manner and nanoparticles were found to localize in the cytosol. Further, the nanoparticles exhibited excellent negative contrast in magnetic resonance imaging (MRI) experiments and with no cytoxicity (5-100 μg/mL iron oxide nanoparticles) to both normal as well as cancer cells demonstrating its biocompatibility. Thus, this novel material integrates the ability to image tissues with high sensitivity by MRI and specifically visualize Y79 retinoblastoma cells by fluorescence imaging with no toxicity.
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